How Human Antibodies Block the Immune System's Off-Switch
Abgenix's 1999 patent on fully human monoclonal antibodies that bind to CTLA-4, a protein brake on the immune system, allowing T-cells to stay active and attack cancer cells.
Original patent title: “Human monoclonal antibodies to CTLA-4”
Abgenix's 1999 patent on fully human monoclonal antibodies that bind to CTLA-4, a protein brake on the immune system, allowing T-cells to stay active and attack cancer cells. Granted to Abgenix Inc in 2004 with 123 claims and 500 forward citations.
Key facts
Coverage
What does this patent actually cover?
This patent claimsclaimsThe numbered statements at the end of a patent that legally define what the inventor owns.Read more → a fully human monoclonal antibody that targets CTLA-4, a receptor on T-cells that acts as an off-switch for the immune system. According to ClaimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1, the antibody uses a specific human gene sequence (VH 3-33 family) with key amino acid mutations to bind tightly to CTLA-4. Claim 4 specifies that the antibody must bind with high affinity (at least 10^-9 M) and be highly selective—at least 100 times more attracted to CTLA-4 than to similar proteins like CD28 or B7-2. By binding to CTLA-4, the antibody blocks it from interacting with its natural partners (B7-1 and B7-2), which prevents the immune system from shutting down. An example of its action is boosting the production of Interleukin-2 (IL-2), a signaling molecule that tells T-cells to multiply and fight.
The gap
What does this patent NOT cover?
- Does not cover antibodies derived from mice or other non-human animals that have not been fully humanized.
- Does not cover antibodies that bind to CTLA-4 but also cross-react with lower mammals like mice, rats, or rabbits.
- Does not cover antibodies with low binding affinity weaker than 10^-9 M or poor selectivity less than 100:1 over CD28.
- Does not cover therapies that target the CTLA-4 pathway using non-antibody molecules, such as small-molecule drugs or soluble receptor proteins.
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
What made this novel
Instead of just finding any antibody that binds CTLA-4, the inventors engineered a fully human antibody that is highly selective against closely related proteins like CD28. This selectivity is crucial because CD28 is the 'on-switch' for T-cells; blocking it would accidentally shut down the immune response instead of boosting it.
Schematic visualization of the patent's claim structure. Hand-drawn diagrams in progress for each landmark patent.
Where you've seen this
Real-world examples
Tremelimumab (Imjudo), an FDA-approved immunotherapy drug for liver and lung cancer.
XenoMouse technology platforms used to generate fully human antibodies.
Why it matters
The bigger picture
This patent represents a foundational step in cancer immunotherapy. By blocking CTLA-4, it paved the way for drugs like tremelimumab to treat cancers like mesothelioma and non-small cell lung cancer by keeping the patient's own immune system active against tumors.
Filed
December 23, 1999
Granted
January 27, 2004
Market context
Who's building on this
Companies in this space
AstraZeneca and Pfizer built directly on this technology to develop and commercialize tremelimumab. Amgen, which acquired Abgenix in 2007, continues to utilize the underlying Xenomouse platform to generate human monoclonal antibodies.
Market impact
This patent protected key intellectual property for the second major CTLA-4 antibody class (tremelimumab), establishing a competitive landscape alongside Bristol Myers Squibb's ipilimumab (Yervoy) and helping to launch the multi-billion dollar checkpoint inhibitor market.
Claim 1 — Plain English
What this patent covers
This patent claims a fully human monoclonal antibody that targets CTLA-4, a receptor on T-cells that acts as an off-switch for the immune system. According to Claim 1, the antibody uses a specific human gene sequence (VH 3-33 family) with key amino acid mutations to bind tightly to CTLA-4. Claim 4 specifies that the antibody must bind with high affinity (at least 10^-9 M) and be highly selective—at least 100 times more attracted to CTLA-4 than to similar proteins like CD28 or B7-2. By binding to CTLA-4, the antibody blocks it from interacting with its natural partners (B7-1 and B7-2), which prevents the immune system from shutting down. An example of its action is boosting the production of Interleukin-2 (IL-2), a signaling molecule that tells T-cells to multiply and fight.
The clever bit
Instead of just finding any antibody that binds CTLA-4, the inventors engineered a fully human antibody that is highly selective against closely related proteins like CD28. This selectivity is crucial because CD28 is the 'on-switch' for T-cells; blocking it would accidentally shut down the immune response instead of boosting it.
What it does not cover
- Does not cover antibodies derived from mice or other non-human animals that have not been fully humanized.
- Does not cover antibodies that bind to CTLA-4 but also cross-react with lower mammals like mice, rats, or rabbits.
- Does not cover antibodies with low binding affinity weaker than 10^-9 M or poor selectivity less than 100:1 over CD28.
- Does not cover therapies that target the CTLA-4 pathway using non-antibody molecules, such as small-molecule drugs or soluble receptor proteins.
Patent timeline
Application submitted to the patent office
Application published, typically 18 months after filing
Patent officially issued
PatentBrief Score
Impact Score
High impact
Citation count
40/40
Highly cited
Claim breadth
20/20
Very broad protection
Recency
0/20
Older than 20 years
Assignee scale
20/20
Major company or institution
PatentBrief Impact Score — based on citation count, claim breadth, recency, and assignee scale. Not a legal assessment.
Heuristic Value Estimate
What this patent might be worth
$270K – $864K
Midpoint $540K · expired or expiring · industry ×3.0
Heuristic only — blends forward/backward citation counts, claim scope, time remaining, litigation history, and CPC-derived industry baseline. Real valuations need a professional appraisal.
The original legal language
Original claims
123 claims as filed with the patent office.
Concepts involved
Citations
Patent lineage
Cite this patent
Corvalan, J. R., Gilman, S. C., Davis, C. G., Neveu, M. J., Hanson, D. C., Mueller, E. E., & Hanke, J. H. (2004). How Human Antibodies Block the Immune System's Off-Switch (U.S. Patent No. 6,682,736). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/6682736/enbrel-etanercept
Auto-generated from the patent record. Double-check author order and the issue date against the official USPTO document before submitting.
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Common Questions
Frequently Asked Questions
What does How Human Antibodies Block the Immune System's Off-Switch cover?
Abgenix's 1999 patent on fully human monoclonal antibodies that bind to CTLA-4, a protein brake on the immune system, allowing T-cells to stay active and attack cancer cells.
Who owns patent US 6682736?
Abgenix Inc owns this patent, granted in 2004.
When does this patent expire?
This patent has expired and is now in the public domain — anyone can use the invention freely.
What is patent US 6682736 cited by?
This patent has been cited by 500 later patents that build on its ideas.
What problem does this patent solve?
This patent represents a foundational step in cancer immunotherapy. By blocking CTLA-4, it paved the way for drugs like tremelimumab to treat cancers like mesothelioma and non-small cell lung cancer by keeping the patient's own immune system active against tumors.
What does this patent NOT cover?
Does not cover antibodies derived from mice or other non-human animals that have not been fully humanized.
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